Neurotransmitter receptors; adrenergic (beta1, beta2, alpha1 and alpha2), cholinergic (muscarinic and nicotinic), dopaminergic, and serotonergic receptors are being isolated and purified in order to understand the molecular basis of receptor function and neuronal communication. Specific projects are underway to provide precise structural information on each of the above receptor proteins. Structural data being obtained include primary sequence data, proteolytic digest maps, topology information and structure-function data, e.g. neurotransmitter binding site localization, sugar localization, membrane domain and effector coupling protein recognition domains. Our data have demonstrated that structural similarities exist amongst non-pharmacologically related neurotransmitter receptors (muscarinic, cholinergic and alpha adrenergic) and that these neurotransmitter receptors mediate cellular modulation via protein conformational changes initiated by neurotransmitter binding to the binding site in the extracellular protein domain. Receptor coupling is mediated by the cytoplasmic "tail" of the receptors which appears to be the effector protein (GTP-regulatory protein) recognition portion of the receptor. Protein preparative procedures have been established which include various HPLC steps, ligand affinity chromatography, monoclonal antibody affinity chromatography, preparative SDS-gel electrophoresis, lectin affinity chromatography, ion exchange chromatography and column isoelectric focusing. The establishment of these purification protocols are now permitting simultaneous detailed structural comparisons of all adrenergic and cholinergic receptor proteins. Functional receptor proteins isolated by affinity chromatography and HPLC are being reconstituted into phospholipid vesicles together with purified GTP-regulatory proteins (Gi and Go) to study molecular events involved in the control of cellular events by receptor proteins.